Izzi Gengaro

All Publications

• Precision epigenetic editing: Technological advances, enduring challenges, and therapeutic applications. Cell chemical biology Roth, G. V., Gengaro, I. R., Qi, L. S. 2024

  Abstract

  The epigenome is a complex framework through which gene expression is precisely and flexibly modulated to incorporate heritable memory and responses to environmental stimuli. It governs diverse cellular processes, including cell fate, disease, and aging. The need to understand this system and precisely control gene expression outputs for therapeutic purposes has precipitated the development of a diverse set of epigenetic editing tools. Here, we review the existing toolbox for targeted epigenetic editing, technical considerations of the current technologies, and opportunities for future development. We describe applications of therapeutic epigenetic editing and their potential for treating disease, with a discussion of ongoing delivery challenges that impede certain clinical interventions, particularly in the brain. With simultaneous advancements in available engineering tools and appropriate delivery technologies, we predict that epigenetic editing will increasingly cement itself as a powerful approach for safely treating a wide range of disorders in all tissues of the body.

  View details for DOI 10.1016/j.chembiol.2024.07.007

  View details for PubMedID 39137782

• Persistent in vivo epigenetic silencing of Pcsk9. Cell research Gengaro, I. R., Qi, L. S. 2024

  View details for DOI 10.1038/s41422-024-00954-z

  View details for PubMedID 38565654

• Modular development enables rapid design of media for alternative hosts BIOTECHNOLOGY AND BIOENGINEERING Biedermann, A. M., Gengaro, I. R., Rodriguez-Aponte, S. A., Love, K. R., Love, J. 2022; 119 (1): 59-71

  Abstract

  Developing media to sustain cell growth and production is an essential and ongoing activity in bioprocess development. Modifications to media can often address host or product-specific challenges, such as low productivity or poor product quality. For other applications, systematic design of new media can facilitate the adoption of new industrially relevant alternative hosts. Despite manifold existing methods, common approaches for optimization often remain time and labor-intensive. We present here a novel approach to conventional media blending that leverages stable, simple, concentrated stock solutions to enable rapid improvement of measurable phenotypes of interest. We applied this modular methodology to generate high-performing media for two phenotypes of interest: biomass accumulation and heterologous protein production, using high-throughput, milliliter-scale batch fermentations of Pichia pastoris as a model system. In addition to these examples, we also created a flexible open-source package for modular blending automation on a low-cost liquid handling system to facilitate wide use of this method. Our modular blending method enables rapid, flexible media development, requiring minimal labor investment and prior knowledge of the host organism, and should enable developing improved media for other hosts and phenotypes of interest.

  View details for DOI 10.1002/bit.27947

  View details for Web of Science ID 000708099600001

  View details for PubMedID 34596238

  View details for PubMedCentralID PMC9298315

• Self-entanglement of a tumbled circular chain PHYSICAL REVIEW RESEARCH Soh, B. W., Gengaro, I. R., Klotz, A. R., Doyle, P. S. 2019; 1 (3)

  View details for DOI 10.1103/PhysRevResearch.1.033194

  View details for Web of Science ID 000600661600002